High-intensity versus low-level laser in musculoskeletal disorders

Purpose To evaluate the current evidence comparing low level to high level laser therapy to reveal any superiorities in the treatment of musculoskeletal disorders. Methods Five databases were searched till September 2022 to obtain relevant RCTs comparing high intensity and low-level laser therapies in the management of musculoskeletal disorders. Two authors assessed the methodological quality of the included studies using the Physiotherapy Evidence Database scale and meta-analysis was conducted for studies that showed homogeneity. Results Twelve articles were included in this systematic review with a total population of 704 participants across various musculoskeletal pathologies including tennis elbow, carpal tunnel syndrome, chronic non-specific low back pain, knee arthritis, plantar fasciitis, and subacromial impingement. There were no statistical differences between the two interventions in pain, electrophysiological parameters, level of disability, quality of life, postural sway or pressure algometer, however, Low level laser therapy showed superiority in increasing grip strength compared to high intensity laser therapy while results were significant in favour of high intensity laser therapy regarding long head of biceps diameter and cross sectional area, supraspinatus thickness and echogenicity and acromio-humeral distance. Conclusion The current literature suggests no superiority of both types of laser therapy in musculoskeletal disorders, however, more RCTs with larger sample size are required to reach a definitive conclusion regarding the superiority of either form of laser therapy in musculoskeletal disorders.


Introduction
Musculoskeletal disorders (MSD) are injuries and dysfunctions that have a negative impact on the human musculoskeletal system.They are the most common cause of Based on the latest analysis of the Global Burden of Disease data for 2019, there are globally about 1.71 billion people living with musculoskeletal diseases, including neck pain, low back pain, osteoarthritis, fractures, rheumatoid arthritis, and amputations [4].Therefore, musculoskeletal problems are among the most significant contributors to the demand for rehabilitation therapy [4].
Different non-pharmacological interventions have been used in the management of MSD including acupuncture, exercise, manual therapy, and different physical therapy modalities [5].One of the most important treatment methods that have been used as non-surgical treatments and painless methods for managing a wide range of MSD is laser therapy including low-level laser therapy (LLLT) and highintensity laser therapy (HILT).
Low-intensity lasers can treat painful inflammatory conditions by lowering levels of biochemical markers, oxidative stress, neutrophil cell flow, and edema formation.It is therefore extensively used to treat acute and chronic painful conditions such as carpal tunnel syndrome, rheumatoid arthritis, knee inflammation, and injuries [6][7][8].
Low-intensity lasers can also alleviate pain by stimulating endorphin release and altering nerve excitation and conduction in peripheral nerves [9].Besides its ability to regulate the functional characteristics of affected areas by promoting microcirculation and accelerating lateral circulation [10].In addition, LLLT stimulates fibroblast proliferation and collagen synthesis which facilitate the healing process of tendon tissue after injury [11,12].
Another form of laser therapy for controlling MSD is HILT, which is a novel form of laser therapy that has just emerged with unique properties such as an emission wavelength of 1,064 nm and a maximum output power of 3,000 W [13].The high-intensity laser's wavelength allows it to work with more focused and intense light energy, with a further increase in the concentration of endogenous chromophores during the treatment program.
In addition to its ability to diffuse more in tissues and for a deeper distance, it creates ATP and RNA, promotes the oxidative response to mitochondria, improves photo-biological effects on damaged tissues, and stimulates collagen synthesis in muscle tendons [14].It has been reported that HILT applications have a significant effect on the recovery of nerve paralysis [13], wound repair [15], and pain relief [14].
Previous studies examined the separate effects of LLLT and HILT in the management of musculoskeletal disorders [16,17].However, based on the authors' knowledge, no previous systematic review has examined the effect of HILT versus low LLLT in the management of musculoskeletal disorders.Therefore, this systematic review and meta-analysis aim to fill this gap and provide clear evidence regarding the superiority of either HILT or LLLT in clinical practice.

Methods
This systematic review was registered in September 2022 in PROSPERO database record number CRD42022360797 and the authors adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA 2020) [18].

Information sources and search strategy
A systematic search was conducted across five databases from inception to September 2022 searching for randomized controlled trials of a population suffering from any musculoskeletal disorders such as low back pain, knee osteoarthritis, plantar fasciitis, or elbow lateral epicondylitis.Participants received HILT compared to LLLT and outcome measures included any motor or sensory outcomes.Articles that have not been peer-reviewed and non-English written articles were excluded from this review Appendix 1.

Study selection
The initial search results were imported and went through duplicate checking using Mendeley software.Two researchers independently screened titles and abstracts of the included articles using Rayyan web-based tool [19].
Full-text filtration process was conducted via another two authors.The senior author resolved any conflict in the filtration process.

Quality assessment
The Physiotherapy Evidence Database (PEDro) scale [20] was used to assess the methodological quality of the included studies, the process was conducted by two authors independently.The PEDro Scale consists of 11 criteria where only ten criteria were calculated in the total score.The scored articles were considered to be of high quality, good quality, or fair quality if the score was from 9 to 10, 6-8, or from 4 to 5 respectively.The senior author was consulted in case of disagreements in the quality assessment process.

Data collection process
The studies' population and administered intervention data were extracted by two authors.Also, the results, outcome measures and domains were summarized into the data extraction sheet.

Data synthesis
We conducted the meta-analysis through Cochrane Collaboration's software Review Manager (RevMan version 5.3, Copenhagen).The post treatment scores were obtained in terms of mean and standard deviation for the pooled estimate.Data were combined as standardized mean differences (SMD) with 95% confidence intervals (CI).To solve the heterogeneity between included studies, I 2 statistic was used.A percentage of ≥ 75% resembles considerable heterogeneity while a percentage of ≤ 40% reflects no heterogeneity of importance.A narrative description of the review finding will be elucidated if meta-analysis was not possible.The meta-analysis used the random-effect model, and its results were expressed as pooled effects, with corresponding 95% CIs and P values.

Study selection
Figure (1) shows the flow of the selection process throughout the study, an electronic search was conducted from inception till September 2022.The search study retrieved 56 records in PubMed, 74 in PEDro, 310 in Scopus, 116 in Google Scholar, 79 in Cochrane library, and 111 in Web of Science.After the removal of 74 duplicates, titles and abstracts of 598 study were screened.Twenty four studies underwent the phase of full text screening after the exclusion of 574.Initially, eight protocols were excluded because their full text papers have not been published yet.Three other studies were excluded due to the inappropriateness of intervention, population or design.The last study was excluded because it was not published in English.

Quality appraisal
The twelve articles included were assessed with the PEDro scale.Two studies had a fair quality [21,22], eight studies [23][24][25][26][27][28][29][30] deemed to be of a good quality, and the other two studies [31,32] were assessed to be of an excellent quality.Throughout the 12 included studies, the main weakness points were regarding participants', assessors', and therapists' blinding.Only half of the studies [21,24,25,29,31,32] managed to blind the participants, while Ordahan et al. [30] was the only study that blinded the therapists.

Characteristics of the included studies
We included a total of 12 articles, that fulfilled our inclusion criteria, and were described in Table (1).The studies' publication date ranged from 2014 to 2021, with a total sample of 704 participants, and a range between 16 and 109 throughout the studies, with an average age range from 18 to 75.The RCTs included patients with various musculoskeletal pathologies; two studies [21,32] included participants with tennis elbow disorders, three studies encompassed patients suffering from carpal tunnel syndrome, [23,27,31] two studies [25,26] comprised people with chronic non-specific low back pain, two studies [22,24] included participants with knee arthritis, two studies [29,30] dealt with patients with unilateral plantar fasciitis, and the last study [28] included patients with subacromial impingement Table (2).
The included papers vary according to intervention strategies with differences in the duration of application, wavelength, power and frequency.The total duration of the treatment varied from five sessions over two weeks [26] to 24 sessions over 12 weeks [31].   1 3

Ultra-sonographic parameters
Two studies [28,29] measured long head of biceps diameter and cross sectional area, supraspinatus thickness and echogenicity, acromio-humeral distance which were significant in favour of HLLT, however, plantar fascia thickness was not significant between groups.

Electrophysiological parameters
Three studies [23,27,31] measured respectively sensory nerve action potential (SNAP), compound muscle action potential (CMAP), SNAP peak latency and amplitude, CMAP onset latency and amplitude, combined sensory index, sensory nerve conduction velocity, distal motor latency revealing no significant between HILT and LLLT.

Disability scales
Several measurement scales were used in order to demonstrate the level of disability using the following, shoulder pain and disability index for subacromial impingement [28], quick disability of arm, shoulder and hand for lateral epicondylitis [32], western Ontario and McMaster universities osteoarthritis index for knee osteoarthritis (WOMAC) [24], oswestry disability index for low back pain [26], foot and ankle outcome scales for plantar fasciitis [30] and boston symptoms severity scale for carpal tunnel syndrome [23].
However, all of them reported non-significant differences between both interventions except for the WOMAC scale which was significant for the HILT group.

Pain
Nine studies [21,23,24,26,[28][29][30][31][32] examined the efficacy of HILT vs. LLLT in reducing pain using VAS in patients with subacromial impingement, carpal tunnel syndrome, knee osteoarthritis, plantar fasciitis and lateral elbow pain, and they reported no significance difference between both groups except for kheshie et al. [24] which reported a significant difference for the HILT group.Additionally, one study [30] used heel tenderness index to assess pain among patients with plantar fasciitis without revealing different results.These results are supported by a quantitative analysis for two studies [21,32] which showed a non-statistical significance difference between both interventions, SMD − 0.37 (-1.05,0.32,P = 0.29) Fig. (2).

Hand grip strength
Based on a quantitative analysis, two studies [21,32] showed that LLLT is favourable over HILT in improving grip strength measured by dynamometer SMD,4,32 (0.99,7.65,P = 0.01) Fig. (3).significant effect in favor of the HILT.However, the other two studies conducted on the same targeted population [23,27] were not significant.This may be due to the larger population i.e., 98 participants and the longer duration of treatment in Ezzati et al., 2020 that exceeded the other two studies with a range of 100 to 250 s.
Moving to the level of disability, only two studies [24,32] out of five revealed significant difference between the two types of laser therapy in favour of HILT however, this difference was marginal in one of them (p = 0.046) while the improvement of level of disability in the other study may be linked to the pain reduction in the HILT group compared to the LLLT, hence, the level of disability would probably decrease more than the other group.
Similarly, the quality of life scores of the same study [32] were significant regarding physical component which may be linked to the improvement of grip strength in such population i.e., patients with lateral epicondylitis.In contrast, the quality of life in patients with chronic low back pain was not significant as the pain level did not show any difference [26].
Compared to previously reported results, LLLT and HILT are considered as effective modalities in reducing musculoskeletal pain [16,17].Furthermore, both modalities are effective in the management of knee osteoarthritis when it comes to knee pain and function outcomes [34].However, due to the originality of the research question, no previous systematic review examined the comparative efficacy of both interventions, therefore, reported results cannot be compared with other studies.
A number of limitations could be noted in this review.Due to the novelty of our idea, we could not compare our results with other reviews as it is the first one which evaluates the comparative efficacy of HILT versus LLLT among individuals with musculoskeletal disorders.Furthermore, limited number of randomized clinical trials were found which compared the efficacy of HILT to LLLT in among musculoskeletal diseases, and this limited the ability to formulate a strong evidence to prefer one of the both interventions over the other in addition to the applicability of performing meta-analysis which was only possible in only two studies sharing the same characteristics as the rest of the studies were heterogeneous regarding the population and the measured outcomes.

Conclusion
There is insufficient evidence concerning the superiority of HILT therapy over LLLT in patients with musculoskeletal diseases due to the lack of large number of randomized controlled trials with adequate sample size.However, both

Quality of life scales
Two measurement scales short form health survey (SF-36) [32] and EuroQol [26] were used to evaluate the efficacy of HILT versus LLLT in improving life quality in patients with lateral epicondylitis and low back pain respectively, and both results were not significant between both groups.

Postural sway parameters
One study [25] compared HILT versus LLLT in improving postural control parameters in patients with chronic non-specific low back pain, and it showed no significance between both interventions.

Algometer measures
Two studies [21,30] used the pressure algometer device to evaluate the efficacy of both interventions in enhancing the tenderness threshold in patients with lateral epicondylitis and plantar fasciitis.According to their reports, there was no advantage for any of the administered interventions.

Discussion
This systematic review of randomized controlled trial revealed LLLT has a significant effect on grip strength of patients with lateral epicondylitis compared to HILT however no statistically significant difference between HILT and LLLT in terms of musculoskeletal pain reduction while the results were conflicting concerning level of disability, quality of life and electrophysiological parameters such as the amplitude and latency of both CMAP and SNAP obtained from patients with carpal tunnel syndrome.
The improvement of grip strength in the LLLT group may be attributed to the increase of ATP, collagen production and the facilitation of healing induced by LLLT which in turn increase the designated muscles' power and grip strength [33].
The results of no superiority of any of the investigated intervention in terms of pain contradict with the previous results reported by Kheshie et al., 2014 which demonstrated significant effects of HILT in pain reduction compared to LLLT, this may be due to the different population investigated i.e., patients with knee osteoarthritis and the ability of the HILT to penetrate deeply in the anatomical configuration of the treated joint.
Regarding electrophysiological parameters, Ezzati et al., 2020 [31] which measured CMAP amplitude and latency and SNAP amplitude and latency of the median nerve groups in patients with carpal tunnel syndrome reported a 1 3

Fig. 1
Fig. 1 PRISMA flowchart of studies search and selection

Table 1
Quality assessment scores

Table 2
Population characteristics of the included studies